Effect of Evogliptin on the Progression of Aortic Valvular Calcification.

BACKGROUND: Medical therapy for aortic stenosis (AS) remains an elusive goal. OBJECTIVES: This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression. METHODS: A total of 228 patients (age 67 ± 11 years; 33% women) with AS were randomly assigned to receive placebo (n = 75), evogliptin 5 mg (n = 77), or evogliptin 10 mg (n = 76). The primary endpoint was the 96-week change in aortic valve calcium volume (AVCV) on computed tomography. Secondary endpoints included the 48-week change in active calcification volume measured using 18F-sodium fluoride positron emission tomography (18F-NaF PET). RESULTS: There were no significant differences in the 96-week changes in AVCV between evogliptin 5 mg and placebo (-5.27; 95% CI: -55.36 to 44.82; P = 0.84) or evogliptin 10 mg and placebo (-18.83; 95% CI: -32.43 to 70.10; P = 0.47). In the placebo group, the increase in AVCV between 48 weeks and 96 weeks was higher than that between baseline and 48 weeks (136 mm3; 95% CI: 108-163 vs 102 mm3; 95% CI: 75-129; P = 0.0485). This increasing trend in the second half of the study was suppressed in both evogliptin groups. The 48-week change in active calcification volume on 18F-NaF PET was significantly lower in both the evogliptin 5 mg (-1,325.6; 95% CI: -2,285.9 to -365.4; P = 0.008) and 10-mg groups (-1,582.2; 95% CI: -2,610.8 to -553.5; P = 0.0038) compared with the placebo group. CONCLUSIONS: This exploratory study did not demonstrate the protective effect of evogliptin on AV calcification. Favorable 18F-NaF PET results and possible suppression of aortic valve calcification with longer medication use in the evogliptin groups suggest the need for larger confirmatory trials. (A Multicenter, Double-blind, Placebo-controlled, Stratified-randomized, Parallel, Therapeutic Exploratory Clinical Study to Evaluate the Efficacy and Safety of DA-1229 in Patients With Calcific Aortic Valve Disease; NCT04055883).

Impact of Balloon-Expandable TAVR Valve Deformation and Calcium Distribution on Outcomes in Bicuspid Aortic Valve.

BACKGROUND: Research on the role of transcatheter heart valve (THV) deformation and calcium distribution in patients with bicuspid aortic valves (BAVs) undergoing transcatheter aortic valve replacement (TAVR) remains limited. OBJECTIVES: The aim of this study was to evaluate the impact of THV deformation on clinical outcomes in individuals with BAVs undergoing TAVR and the influence of calcium on these outcomes. METHODS: In total, 229 consecutive patients with BAVs who underwent TAVR with balloon-expandable valves and had computed tomography (CT) performed 30 days post-TAVR were analyzed. Patients were stratified into 3 groups: group 1 (n = 125), with no THV underexpansion or eccentricity; group 2 (n = 69), with underexpansion or eccentricity; and group 3 (n = 35), with both. Calcium distribution was assessed using CT, and its associations with clinical outcomes, including all-cause mortality at 3 years and leaflet thrombosis at 30 days, were determined. A subgroup analysis of patients with type 1 BAVs was conducted. RESULTS: Group 3 exhibited higher rates of all-cause mortality than the other groups, along with the highest risk for hypoattenuated leaflet thickening at 30 days. Multivariate analysis identified annular and left ventricular outflow tract calcification as independent predictors of all-cause mortality and hypoattenuated leaflet thickening. In patients with type 1 BAVs, excessive calcification at the raphe and opposite leaflet were associated with all-cause mortality at 3 years. CONCLUSIONS: THV deformation post-TAVR was significantly linked to all-cause mortality in patients with BAVs. Annular and left ventricular outflow tract calcification correlated with increased risks for all-cause mortality and leaflet thrombosis. (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Thrombosis and Its Treatment With Anticoagulation [RESOLVE]; NCT02318342).

Management of Fluid Overload in Patients With Severe Aortic Stenosis (EASE-TAVR): A Randomized Controlled Trial.

BACKGROUND: Fluid overload (FO) subjects patients with severe aortic stenosis (AS) to increased risk for heart failure and death after valve replacement and can be objectively quantified using bioimpedance spectroscopy (BIS). OBJECTIVES: The authors hypothesized that in AS patients with concomitant FO, BIS-guided decongestion could improve prognosis and quality of life following transcatheter aortic valve replacement (TAVR). METHODS: This randomized, controlled trial enrolled 232 patients with severe AS scheduled for TAVR. FO was defined using a portable whole-body BIS device according to previously established cutoffs (≥1.0 L and/or ≥7%). Patients with FO (n = 111) were randomly assigned 1:1 to receive BIS-guided decongestion (n = 55) or decongestion by clinical judgment alone (n = 56) following TAVR. Patients without FO (n = 121) served as a control cohort. The primary endpoint was the composite of hospitalization for heart failure and/or all-cause death at 12 months. The secondary endpoint was the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire. RESULTS: The occurrence of the primary endpoint at 12 months was significantly lower in the BIS-guided vs the non-BIS-guided decongestion group (7/55 [12.7%, all deaths] vs 18/56 [32.1%, 9 hospitalizations for heart failure and 9 deaths]; HR: 0.36; 95% CI: 0.15-0.87; absolute risk reduction = -19.4%). Outcomes in the BIS-guided decongestion group were identical to the euvolemic control group (log-rank test, P = 0.7). BIS-guided decongestion was also associated with a higher increase in the Kansas City Cardiomyopathy Questionnaire score from baseline compared to non-BIS-guided decongestion (P = 0.001). CONCLUSIONS: In patients with severe AS and concomitant FO, quantitatively guided decongestive treatment and associated intensified management post-TAVR was associated with improved outcomes and quality of life compared to decongestion by clinical judgment alone. (Management of Fluid Overload in Patients Scheduled for Transcatheter Aortic Valve Replacement [EASE-TAVR]; NCT04556123).

Asymmetrical Expansion of Balloon-Expandable Transcatheter Aortic Valve Prostheses: Implications for Valve Hemodynamic and Clinical Outcomes.

BACKGROUND: Asymmetrical expansion of transcatheter heart valves (THVs), manifesting as stent frame deformation, is an occasional fluoroscopic finding in transcatheter aortic valve replacement (TAVR). OBJECTIVES: The aim of this study was to investigate the impact of asymmetrical expansion of balloon-expandable THVs on hemodynamic valve performance and clinical outcomes. METHODS: In a prospective registry, TAVR asymmetry index was measured using freeze-frame fluoroscopic images and was defined as the ratio of THV heights: [(longer height/shorter height) - 1] × 100. THV hemodynamic performance was measured using echocardiography before hospital discharge. Impaired hemodynamic valve performance was defined as a mean residual THV gradient ≥20 mm Hg and/or moderate or greater paravalvular regurgitation. RESULTS: Among 1,216 patients undergoing transfemoral TAVR for native severe aortic valve stenosis with contemporary balloon-expandable THVs between February 2014 and June 2022, asymmetry index was an excellent predictor of impaired hemodynamic valve performance (area under the receiver-operating characteristic curve: 0.88; 95% CI: 0.84-0.92; P < 0.001). The optimal asymmetry index threshold for predicting impaired THV performance was >5.5% (sensitivity 77%, specificity 86%) and occurred in 17% of patients. Higher asymmetry index, as a continuous variable, was associated with impaired hemodynamic valve performance independent of total aortic valve calcium, bicuspid anatomy, balloon-expandable valve prosthesis type or size, and Society of Thoracic Surgeons Predicted Risk of Mortality score (OR: 1.37; 95% CI: 1.29-1.46; P < 0.001). High TAVR asymmetry index was not associated with all-cause mortality during a median of 376 days of follow-up (HR: 1.00; 95% CI: 0.71-1.41; P = 0.989). CONCLUSIONS: Asymmetrical expansion of balloon-expandable THVs was associated with impaired hemodynamic valve performance but not with clinical outcomes.

Outcomes of transcatheter aortic valve implantation for native aortic valve regurgitation.

BACKGROUND: Large datasets of transcatheter aortic valve implantation (TAVI) for pure aortic valve regurgitation (PAVR) are scarce. AIMS: We aimed to report procedural safety and long-term clinical events (CE) in a contemporary cohort of PAVR patients treated with new-generation devices (NGD). METHODS: Patients with grade III/IV PAVR enrolled in the FRANCE-TAVI Registry were selected. The primary safety endpoint was technical success (TS) according to Valve Academic Research Consortium 3 criteria. The co-primary endpoint was defined as a composite of mortality, heart failure hospitalisation and valve reintervention at last follow-up. RESULTS: From 2015 to 2021, 227 individuals (64.3% males, median age 81.0 [interquartile range {IQR} 73.5-85.0] years, with EuroSCORE II 6.0% [IQR 4.0-10.9]) from 41 centres underwent TAVI with NGD, using either self-expanding (55.1%) or balloon-expandable valves (44.9%; p=0.50). TS was 85.5%, with a non-significant trend towards increased TS in high-volume activity centres. A second valve implantation (SVI) was needed in 8.8% of patients, independent of valve type (p=0.82). Device size was ≥29 mm in 73.0% of patients, post-procedure grade ≥III residual aortic regurgitation was rare (1.2%), and the permanent pacemaker implantation (PPI) rate was 36.0%. At 30 days, the incidences of mortality and reintervention were 8.4% and 3.5%, respectively. The co-primary endpoint reached 41.6% (IQR 34.4-49.6) at 1 year, increased up to 61.8% (IQR 52.4-71.2) at 4 years, and was independently predicted by TS, with a hazard ratio of 0.45 (95% confidence interval: 0.27-0.76); p=0.003. CONCLUSIONS: TAVI with NGD in PAVR patients is efficient and reasonably safe. Preventing the need for an SVI embodies the major technical challenge. Larger implanted valves may have limited this complication, outweighing the increased risk of PPI. Despite successful TAVI, PAVR patients experience frequent CE at long-term follow-up.

Aortic regurgitation: from mechanisms to management.

Aortic regurgitation (AR) is a common clinical disease associated with significant morbidity and mortality. Investigations based largely on non-invasive imaging are pivotal in discerning the severity of disease and its impact on the heart. Advances in technology have contributed to improved risk stratification and to our understanding of the pathophysiology of AR. Surgical aortic valve replacement is the predominant treatment. However, its use is limited to patients with an acceptable surgical risk profile. Transcatheter aortic valve implantation is an alternative treatment. However, this therapy remains in its infancy, and further data and experience are required. This review article on AR describes its prevalence, mechanisms, diagnosis and treatment.

"One-stop" interventional therapy for quadricuspid aortic valve combined with severe coronary artery disease: a case report.

Congenital Quadricuspid Aortic Valve (QAV) malformation is a relatively rare cardiac valve malformation, especially with abnormal coronary opening and severe stenosis of Coronary Artery Disease (CAD). The patient underwent "one-stop" interventional treatment with transcatheter aortic valve replacement and percutaneous coronary stent implantation. Follow up for 12-month with good outcomes.

Resolution of high aortic valve systolic gradient suggesting significant stenosis following closure of patent ductus arteriosus.

A 3-month-old baby girl presenting with heart failure was found to have a large persistent ductus arteriosus as well as a bicuspid aortic valve with severe aortic stenosis. She underwent surgical ductal closure following which there was complete resolution of aortic valve gradients without requiring any aortic valve intervention. This case highlights the importance of understanding hemodynamics in efficacious management of congenital heart disease.

Effect of aortic valve replacement on myocardial perfusion and exercise capacity in patients with severe aortic stenosis.

Aortic valve replacement (AVR) leads to reverse cardiac remodeling in patients with aortic stenosis (AS). The aim of this secondary pooled analysis was to assess the degree and determinants of changes in myocardial perfusion post AVR, and its link with exercise capacity, in patients with severe AS. A total of 68 patients underwent same-day echocardiography and cardiac magnetic resonance imaging with adenosine stress pre and 6-12 months post-AVR. Of these, 50 had matched perfusion data available (age 67 ± 8 years, 86% male, aortic valve peak velocity 4.38 ± 0.63 m/s, aortic valve area index 0.45 ± 0.13cm2/m2). A subgroup of 34 patients underwent a symptom-limited cardiopulmonary exercise test (CPET) to assess maximal exercise capacity (peak VO2). Baseline and post-AVR parameters were compared and linear regression was used to determine associations between baseline variables and change in myocardial perfusion and exercise capacity. Following AVR, stress myocardial blood flow (MBF) increased from 1.56 ± 0.52 mL/min/g to 1.80 ± 0.62 mL/min/g (p < 0.001), with a corresponding 15% increase in myocardial perfusion reserve (MPR) (2.04 ± 0.57 to 2.34 ± 0.68; p = 0.004). Increasing severity of AS, presence of late gadolinium enhancement, lower baseline stress MBF and MPR were associated with a greater improvement in MPR post-AVR. On multivariable analysis low baseline MPR was independently associated with increased MPR post-AVR. There was no significant change in peak VO2 post-AVR, but a significant increase in exercise duration. Change in MPR was associated with change in peak VO2 post AVR (r = 0.346, p = 0.045). Those with the most impaired stress MBF and MPR at baseline demonstrate the greatest improvements in these parameters following AVR and the magnitude of change in MPR correlated with improvement in peak VO2, the gold standard measure of aerobic exercise capacity.

Periprocedural Assessment of Paravalvular Regurgitation After Transcatheter Aortic Valve Replacement Using Diastolic Delta and Videodensitometry.

BACKGROUND: Paravalvular regurgitation (PVR) is a common complication after transcatheter aortic valve replacement, posing an increased risk of heart failure and mortality. Accurate intraprocedural quantification of PVR is challenging. Both hemodynamic indices and videodensitometry can be used for intraprocedural assessment of PVR. We compared the predictive value of the isolated versus combined use of the hemodynamic index diastolic delta (DD) and videodensitometry for the incidence of relevant PVR 1 month after transcatheter aortic valve replacement. METHODS AND RESULTS: In this prospective cohort study, patients underwent periprocedural PVR assessment by DD and videodensitometry (using left ventricular outflow tract-aortic regurgitation [LVOT-AR]). Cardiac magnetic resonance served as reference modality for PVR assessment. Relevant PVR was defined as cardiac magnetic resonance-regurgitant fraction >20%. Fifty-one patients were enrolled in this study. Mean age was 80.6±5.2 years and 45.1% of patients were men. Mean LVOT-AR and cardiac magnetic resonance-regurgitant fraction were 8.2%±7.8% and 11.7%±9.6%, respectively. The correlation between DD and LVOT-AR was weak (r=-0.36). DD and LVOT-AR showed a comparable accuracy to predict relevant PVR (area under the curve 0.82, 95% CI: 0.69-0.95 versus area area under the time-density curve 0.80, 95% CI: 0.62-0.99). The combination of DD and LVOT-AR improved the prediction of relevant PVR (area under the time-density curve, 0.90, 95% CI: 0.81-0.99), and resulted in an increased concordance (86.3%) and positive predictive value (75%) compared with DD alone (76.5% and 40%, respectively), or LVOT-AR alone (82.3% and 50%, respectively). CONCLUSIONS: DD and videodensitometry are both accurate and feasible modalities for the assessment of PVR after transcatheter aortic valve replacement. The synergistic use of both techniques increases the predictive value for relevant PVR after transcatheter aortic valve replacement. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04281771.